title: Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  The serum free light chain (FLC) assay quantitates free kappa (κ) and free lambda (λ) immunoglobulin light chains. This assay has prognostic value in plasma cell proliferative disorders. There are limited data on serum FLC in B-cell malignancies.
  
  
  METHODS
  The association of pretreatment FLC with event-free survival (EFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) was evaluated in 76 patients from the North Central Cancer Treatment Group trial N0489 (NCT00301821) and 219 patients from the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER). Published reference ranges were used to define an elevated FLC or an abnormal κ:λ FLC ratio.
  
  
  RESULTS
  Elevated FLC or abnormal κ:λ FLC ratio was present in 32% and 14% of patients, respectively. Patients with elevated FLC had an inferior OS and EFS in both cohorts compared with patients with normal FLC (N0489: EFS hazard ratio [HR], 3.06; OS HR, 3.16; both P < .02; MER: EFS HR, 2.42; OS HR, 3.40; both P < .001; combined EFS HR, 2.57; OS HR, 3.74; both P < .001). All associations remained significant for EFS and OS after adjusting for the International Prognostic Index (IPI). Abnormal κ:λ FLC ratio was modestly associated with outcome in the combined group (EFS HR, 1.61; OS HR, 1.67; both P = .07), but not in patients without corresponding elevated κ or λ. Elevated FLC was the strongest predictor of outcome in multivariable models with the IPI components.
  
  
  CONCLUSIONS
  Increased serum FLC is an independent, adverse prognostic factor for EFS and OS in DLBCL and warrants further evaluation as a biomarker in DLBCL.
authors.affiliation: Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN 55905, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Ivana N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Katzmann
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Colgan
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Luis F
authors.initials: LF
authors.lastname: Porrata
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Johnston
authors.forename: Grzegorz S
authors.initials: GS
authors.lastname: Nowakowski
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Thompson
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Syrbu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains; D007158:Immunologic Techniques; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains